Obscurin is required for ankyrinB-dependent dystrophin localization and sarcolemma integrity |
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Authors: | Davide Randazzo Emiliana Giacomello Stefania Lorenzini Daniela Rossi Enrico Pierantozzi Bert Blaauw Carlo Reggiani Stephan Lange Angela K Peter Ju Chen Vincenzo Sorrentino |
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Institution: | 1.Molecular Medicine Section, Department of Molecular and Developmental Medicine, and 2.Interuniversitary Institute of Myology, University of Siena, 53100 Siena, Italy;3.Department of Biomedical Sciences, University of Padua, 35137 Padua, Italy;4.University of California, San Diego School of Medicine, La Jolla, CA 92093 |
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Abstract: | Obscurin is a large myofibrillar protein that contains several interacting modules, one of which mediates binding to muscle-specific ankyrins. Interaction between obscurin and the muscle-specific ankyrin sAnk1.5 regulates the organization of the sarcoplasmic reticulum in striated muscles. Additional muscle-specific ankyrin isoforms, ankB and ankG, are localized at the subsarcolemma level, at which they contribute to the organization of dystrophin and β-dystroglycan at costameres. In this paper, we report that in mice deficient for obscurin, ankB was displaced from its localization at the M band, whereas localization of ankG at the Z disk was not affected. In obscurin KO mice, localization at costameres of dystrophin, but not of β-dystroglycan, was altered, and the subsarcolemma microtubule cytoskeleton was disrupted. In addition, these mutant mice displayed marked sarcolemmal fragility and reduced muscle exercise tolerance. Altogether, the results support a model in which obscurin, by targeting ankB at the M band, contributes to the organization of subsarcolemma microtubules, localization of dystrophin at costameres, and maintenance of sarcolemmal integrity. |
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